A mechanism for modulation of cellular responses to VEGF: Activation of the integrins

Many similarities exist in the cellular responses elicited by VEGF and gove rned by integrins. Here, we identify a basis for these interrelationships: VEGF activates integrins. VEGF enhanced cell adhesion, migration, soluble l igand binding, and adenovirus gene transfer mediated by alpha (v)beta (3) a nd also activated other integrins, alpha (v)beta (5), alpha (5)beta (1), an d alpha (2)beta (1), involved in angiogenesis. Certain tumor cells exhibite d high spontaneous adhesion and migration, which were attributable to a VEG F-dependent autocrine/paracrine activation of integrins. This activation wa s mediated by the VEGFR2 receptor and regulated via phosphatidylinositol-3- kinase, Akt, and the PTEN signaling axis. Thus, integrin activation provide s a mechanism for VEGF to induce a broad spectrum of cellular responses.